CN1367018A - Compound preparation of staphylococcolysis enzyme and its preparation method and application - Google Patents
Compound preparation of staphylococcolysis enzyme and its preparation method and application Download PDFInfo
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- CN1367018A CN1367018A CN 02110672 CN02110672A CN1367018A CN 1367018 A CN1367018 A CN 1367018A CN 02110672 CN02110672 CN 02110672 CN 02110672 A CN02110672 A CN 02110672A CN 1367018 A CN1367018 A CN 1367018A
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- Prior art keywords
- preparation
- lysozyme
- lysostaphin
- staphylococcus
- application
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- 238000002360 preparation method Methods 0.000 title claims abstract description 48
- 150000001875 compounds Chemical class 0.000 title claims description 13
- 102000004190 Enzymes Human genes 0.000 title claims description 12
- 108090000790 Enzymes Proteins 0.000 title claims description 12
- 102000016943 Muramidase Human genes 0.000 claims abstract description 37
- 108010014251 Muramidase Proteins 0.000 claims abstract description 37
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 claims abstract description 37
- 235000010335 lysozyme Nutrition 0.000 claims abstract description 36
- 239000004325 lysozyme Substances 0.000 claims abstract description 36
- 229960000274 lysozyme Drugs 0.000 claims abstract description 36
- 108090000988 Lysostaphin Proteins 0.000 claims abstract description 32
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 16
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims abstract description 12
- 241001478240 Coccus Species 0.000 claims abstract description 11
- 241000193998 Streptococcus pneumoniae Species 0.000 claims abstract description 8
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 7
- 241000222122 Candida albicans Species 0.000 claims abstract description 6
- 241000588653 Neisseria Species 0.000 claims abstract description 6
- 229940095731 candida albicans Drugs 0.000 claims abstract description 6
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- 229960002179 ephedrine Drugs 0.000 claims abstract description 6
- 241001537924 Tetracoccus <angiosperm> Species 0.000 claims abstract description 4
- 241000191940 Staphylococcus Species 0.000 claims description 28
- 230000000844 anti-bacterial effect Effects 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 13
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- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 claims description 5
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- 239000011734 sodium Substances 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
The present invention discloses a compounded preparation of lysostaphin and its preparation method and application. Said invented preparation is formeded from lysostaphin, lysozyme, germicide, ion compound, aminoglucose, ephedrine and fresh-keeping agent. It not only can effective kill staphylococcus aureus, candida albicans, gonococcus, chain coccus, anaerobe, pseudomonas aeruginosa, colibacillus, staphylcoccus epidermidis, diplococcus pneumoniae, D group enterocccus, tetracoccus and others, but also can effectively kill drug-fast bacteria of methicillin-resisting staphylococcus aureus, drug-fast diplococcus pneumoniae and others.
Description
Technical field
The class biological preparation that the present invention relates to sterilize, this preparation series is specifically related to compounded technology and the preparation method and the application of staphylococcus lysozyme.
Background technology
The chemical classes therapeutic agent of widely applying is clinically being undertaken the task for the treatment of the caused numerous disease of pathogen microorganism at present.But along with being extensive use of of chemical classes therapeutic agent, many unfavorable factors appear constantly.From the beginning of the nineties, promptly begin both at home and abroad to seek a kind of alternative antibiotic, can play bactericidal effect, but be difficult for producing the biocide preparation of Resistant strain.
Rose in 1993, and had patent and document to mention both at home and abroad and use all kinds of infection of staphylococcus aureus of dissolving staphylococcal bacteria enzyme treatment.Staphylococcus lysozyme itself can be killed staphylococcus aureus and drug resistance gold Portugal bacterium.
Domestic and international patent: US6315996
Topical?lysostaphin?therapy?for?staphylococcus?ocular?infections
The ocular infection that lysostaphin topical therapeutic staphylococcus causes
November 13 calendar year 2001 O ' Callaghan
Board?of?supervisors?of?Louisiana?state?university?and?agricultural
and(baton?rouge，LA)WO0129201
EXPRESSION?OF?RECOMBINANT?MATURE?LYSOSTAPHIN
The expression of recombinant mature lysostaphin
April calendar year 2001 KHATRI GHAN on the 26th SHYAM
BHARAT BIOTECH INTERNATIONAL L (IN India)
AMBIUS6028051
Method?for?the?treatment?of?staphylococcal?disease
The method of the disease that treatment is caused by staphylococcus
On February 22nd, 2000 Climo
AMBIWO9904809
PHARMACEUTICAL?COMPOSITIONS?CONTAINING
LYSOSTAPHIN?ALONE?OR?IN?COMBINATION?WITH?AN
ANTIBIOTIC?FOR?THE?TREATMENT?OF?STAPHYLOCOCCAL
INFECTIONS
The ingredient that contains lysostaphin of treatment staphy lococcus infection (only contains lysostaphin
Or it is compound) with antibiotic
On February 4th, 1999 CLIMO company: AMBIUS5760026
Method?for?treating?mastitis?and?other?staphylococcal?infections
The method of treatment mastitis and other staphy lococcus infections
On June 2nd, 1998 (the earliest since on May 11st, 1987) Blackburn
AMBIDE4425645
New lysostaphin gene with deletion in pro-segment repeat region Deutsche Bundespatent
Delete the novel lysostaphin of initial fragment repeating part gene
HAMMES?WALTER?PROF?DR(DE)；
MUELLER?KARL?GMBH&CO(DE)
Up to the present, countries in the world stay in this field of treatment staphylococcus aureus mostly to staphylococcus lysozyme.And because its enzymatic activity is extremely unstable, be difficult under the room temperature preserve, its range of application is also only at laboratory stage.
At present, except staphylococcus aureus, existing more bacterial antibiotic produces drug resistance, thereby makes that pathogenic bacterial infection is difficult to be effectively controlled.Especially antibiotic improper use, the Resistant strain quantity that is caused is increasing, the infection that these microorganisms cause, and not only curative effect is not good enough or invalid fully under the conventional therapy situation, owing to killed the profitable strain of human body itself, can also change the ecological ragime of patient's normal flora simultaneously.In addition, situation from China's investigation, cross infection is quite serious in the hospital of China, cause extra misery to patient, increase financial burden and misfortune, the primary disease that serious nosocomialtion is suffered from patient can not reach the treatment of expection, even leads to the failure, and produces the sequela be difficult to cure or causes death.
Thereby need a kind of alternative antibiotic, but broad-spectrum sterilization, and the difficult antibacterial that produces endurance strain solves above unfavorable factor.
Summary of the invention
Technical problem to be solved by this invention is to overcome above-mentioned weak point, and a kind of lysostaphin compounded preparation that can make an addition to respectively in external medicine (comprising skin, mucosa), food preservative, health food, disinfectant for external use, the toothpaste is provided.These series of products have safe without toxic side effect, are difficult for producing drug resistance, efficient, broad-spectrum sterilization.
The invention provides a kind of lysostaphin compounded preparation, said preparation is formed 100% form by 0.1-20% staphylococcus lysozyme, 50-85% lysozyme, 1-20% antibacterial, 0.5-20% ionic compound, 0.2-30% glucosamine material, 0-20% ephedrine and 0.1-20% antistaling agent with arbitrary proportion.
The invention discloses lysostaphin compounded preparation, said preparation can make an addition to external medicine, food preservative, oral drugs, ear medicine, nose medicine, fisheries drug, daily use chemicals.
Prescription:
Component ratio staphylococcus lysozyme 0.1-20% lysozyme 50-85% bactericide 1-20% ionic compound 0.5-20% Glucosamine material 0.2-30% ephedrine 0-20% antistaling agent 0.1-20%
A kind of antibacterial can be a kind of in hibitane, the bacteriostatic peptide;
A kind of ionic compound can be K
+, Na
+, Mg
2+, PO
4-, Cl
-In 2 kinds combination;
A kind of glucosamine material can be a kind of in chitin, chitosan, the N-acetyl-D-amino;
A kind of antistaling agent can be a kind of in parabens, the sodium benzoate.
Staphylococcus lysozyme is a kind of bacteriolysin of gram positive bacteria.Form the aminoacid of the tetrapeptide side chain of such gram positive bacteria (for example staphylococcus aureus) whole cell peptidoglycan, be followed successively by the L-alanine, D-glutamic acid, L-lysine, D-alanine; And the first L-alanine links to each other with 3-O-.alpha.-carboxyethyl-D-glucosamine. by an amido link, and the L-lysine that this polysaccharide chains tetrapeptide side chain is the 3rd is attached on the adjacent polysaccharide chains tetrapeptide side chain D-alanine carboxyl by pentapeptide (five glycine) cross-bridge.Intersect in length and breadth thus, about connect and constitute very tough and tensile 3 D stereo loose structure, and aggregate into thicker Peptidoglycan layer.Staphylococcus lysozyme can cut off the Gly-Gly key in the Peptidoglycan.
In order to increase the stability of lysostaphin, enlarge fungicidal spectrum, we have selected lysozyme, β-1,4 glycosidic bond between lysozyme energy cracking-acetylmuramic acid C-1 and the N-acetylglucosamine C-4.Thereby make bactericidal activity stronger, reach the purpose of dissolving and killing bacteria, and can avoid the generation of bacterial drug resistance.
We have selected tens of kinds of micromolecular compounds in addition, through repeated screening, and finally selected a kind of antibacterial such as hibitane, bacteriostatic peptide, a kind of glucosamine material such as chitin, chitosan, N-acetyl-D-amino; A kind of antistaling agent such as parabens, sodium benzoate sodium benzoate.These compositions are composite with different proportionings and above-mentioned 2 kinds of enzymes respectively, add some potassium, sodium, magnesium ion chemical compound simultaneously, and identify the bactericidal effect of the complex that is produced.We find that each compound that is produced not only bactericidal effect is much higher than staphylococcus lysozyme, and 10-40 is doubly to the simple superposition of three's bactericidal effect; The fungicidal spectrum of each complex also obviously enlarges, and all can reach very strong killing action to gram positive bacteria and gram negative bacteria;
Through each complex of verification experimental verification gonococcus, staphylococcus aureus, Candida albicans, bacillus pyocyaneus, escherichia coli, Hemolytic streptococcus are all shown very strong bactericidal action.
Wherein 1% concentration composite lysostaphin formulation soln detects through Shanghai City preventive medicine academy, act on skin surface 2-10 minute after testing and can kill gonococcus, staphylococcus aureus, Candida albicans, bacillus pyocyaneus, escherichia coli, Hemolytic streptococcus etc. rapidly, killing rate reaches 99.9%.Characteristics such as it is good to have bactericidal effect, non-stimulated.
The antibacterial of strain more than 400 that my company entrusts units such as the Huashan, Shanghai City hospital institute of Antibiotics, The 2nd Army Medical College Changhai hospital laboratory, Shanghai City Sixth People's Hospital clinical laboratory, Shanghai City the 9th the People's Hospital clinical laboratory once clinical each section to be collected has carried out the sterilization experiment that presses down of said preparation.Experimental result shows: 1% concentration composite lysostaphin formulation soln is to common clinically staphylococcus aureus, and staphylococcus epidermidis, Diplococcus pneumoniae, D group enterococcus, tetracoccus, product monokaryon Listerella, streptococcus and stomach Helicobacter pylori, escherichia coli, bacillus pyocyaneus etc. all have tangible inhibitory or killing effect.
Pure staphylococcus lysozyme is very unstable at normal temperatures, contains the stabilizing agent and the synergist of multiple our screening in the composite composite lysostaphin, and stability greatly strengthens, and makes it applicable to industrial-scale production.
Staphylococcus lysozyme and composite lysostaphin enzyme are lived stability experiment relatively, preserve 3 months through 37 ℃, see Table 1, table 2.
The activity ratio before and after 37 ℃ of placements in 3 months of table 1 staphylococcus lysozyme
| Enzymatic activity (U/mg) before staphylococcus lysozyme is placed | 37 ℃ of 3 months placement back enzymatic activitys (U/mg) of staphylococcus lysozyme | Rate of descent (%) | |
| ????1 | ????566 | ????301 | ??46.8 |
| ????2 | ????568 | ????299 | ??47.3 |
| ????3 | ????560 | ????290 | ??48.2 |
| Meansigma methods | ??47.4 |
The dissolving staphylococcal bacteria activity ratio before and after 37 ℃ of placements in 3 months of table 2 composite lysostaphin
| Enzymatic activity (U/g) before composite lysostaphin is placed | 37 ℃ of 3 months placement back enzymatic activitys (U/g) of composite lysostaphin | Rate of descent (%) | |
| ????1 | ????1000 | ??????????960 | ??4.00 |
| ????2 | ????1020 | ??????????967 | ??5.20 |
| ????3 | ????1015 | ??????????967 | ??4.73 |
| Meansigma methods | ??4.64 |
Staphylococcus lysozyme enzyme in the composite lysostaphin purer staphylococcus lysozyme height of stability of living as seen from the above table.
Experiment also proves the composite lysostaphin preparation to endurance strain, and as feeling most thorny methicillin-resistant staphylococcus aureus on the present clinical medicine, drug resistance Diplococcus pneumoniae, the effect of having a liking for the narrow food sporangium of Fructus Hordei Germinatus more are better than common antibiotics.
Another technical issues that need to address of the present invention have provided the preparation method of above-mentioned staphylococcus lysozyme compound formulation, this method is in sterilizing room, take by weighing each component by above-mentioned each prescription, add in the clean glass or rustless steel container in proportion successively, stir gently, fully mixed evenly after, fill is in plastics or vial, warehouse-in, room temperature preservation gets final product.
Main Ingredients and Appearance-staphylococcus lysozyme of the present invention, lysozyme, a spot of micromolecular compound comprise sodium benzoate, bacteriostatic peptide, ephedrine, hibitane, ethanol and Mg
2+, Ca
2+, Na
+Deng, can make an addition in the required different product.Said preparation can not produce skin and mucosa to stimulate, and body is not produced any type of toxic and side effects, and can thoroughly degrade by metabolism, do not have residual, can enrichment.
Its basic characteristics are:
1. fungicidal spectrum is wide than staphylococcus lysozyme.Can not only effectively kill staphylococcus aureus, staphylococcus epidermidis, Candida albicans, bacillus pyocyaneus, escherichia coli, Diplococcus pneumoniae, D group enterococcus, tetracoccus, product monokaryon Listerella, streptococcus, anaerobe, have a liking for common malignant bacterias such as the narrow food sporangium of Fructus Hordei Germinatus, gonococcus, stomach Helicobacter pylori are also had very strong killing action.To some drug tolerant bacterias, also demonstrate extremely strong bactericidal effect in addition as drug resistance staphylococcus aureus, drug resistance Diplococcus pneumoniae etc.
2. bactericidal activity and stability are much higher than staphylococcus lysozyme.Because composite lysostaphin is to be main component with the staphylococcus lysozyme, being equipped with compositions such as lysozyme, above-mentioned micromolecular compound and stabilizing agent, synergist is composited, have bigger stability than pure staphylococcus lysozyme, prove that after tested this product can be preserved 2 years at normal temperatures.
3. should be easy to make the mentioned various products of this description by the molten Portugal of series coccus compound enzymic preparation, be applicable to various dosage forms.
The medicine that has added compound enzymic preparation of the present invention can be used for treating abscess, tinea, ulcer, decubital ulcer, burn, scalds, burns, furuncle, incised wound, oral ulcer, vaginitis, all kinds of oral disease, respiratory tract disease and the acute or chronic gastritis that is caused by bacterial infection, the bacterial disease of all kinds of inflammations of external auditory canal, otitis media, keratitis, orbital cellulitis, conjunctivitis, hordeolum, acute and chronic rhinitis, sinusitis, prevention of STD, Aquatic product, prevents and treats acne, all kinds of by antibacterial, fungus-caused skin of face illness etc.; The debridement and the wound dressing that also can be used for preoperative and postoperative in the various surgical operations such as surgery, department of obstetrics and gynecology, urology department, the department of stomatology; Can be used for removing adherent antibacterial on the contact lens.
Complex preparation preparation method of the present invention simply is suitable for large-scale production.
The specific embodiment implements one: make 100 gram composite lysostaphin preparation proportionings: the coccus enzyme 0.1g of Portugal, molten Portugal lysozyme 53g hibitane 1g potassium phosphate 8g sodium chloride 12g chitin 25.9g
Method: in sterilizing room,, add successively in proportion in the clean glass or rustless steel container, stir gently by described each component that takes by weighing of last table, fully mixed evenly after, fill in plastics or vial, warehouse-in, room temperature preservation gets final product.
This proportioning can be used for making mucocutaneous germ killing drugs, and additive capacity is 1-20%.Add the mucocutaneous germ killing drugs of this proportioning, can kill gonococcus, staphylococcus aureus, Candida albicans, bacillus pyocyaneus, escherichia coli of skin, mucomembranous surface etc. in 2-10 minute, killing rate reaches 99.9%.Can treat abscess, tinea, ulcer, decubital ulcer, burn, scald, burn, furuncle, acne, incised wound, oral ulcer, pharyngolaryngitis, gingivitis, vaginitis, prevention of STD, be used for various surgical operations such as surgery, department of obstetrics and gynecology, urology department, the department of stomatology, the debridement of preoperative and postoperative and wound dressing.Implement two: make 100 gram composite lysostaphin preparation proportionings: the coccus enzyme 0.1g of Portugal, molten Portugal lysozyme 52g sodium benzoate 1g potassium phosphate 9g sodium chloride 12g glucose 25.9g
Method: in sterilizing room,, add successively in proportion in the clean glass or rustless steel container, stir gently by described each component that takes by weighing of last table, fully mixed evenly after, fill in plastics or vial, warehouse-in, room temperature preservation gets final product.
This proportioning is used for food fresh keeping, and additive capacity is 1-20%.
Add the food of this proportioning, can prolong the shelf-life of fresh food, can prolong the shelf-life of milk, seafood.Implement three: make 100 gram composite lysostaphin preparation proportionings: the coccus enzyme 0.1g of Portugal, molten Portugal lysozyme 52g bacteriostatic peptide 1g potassium phosphate 9g sodium chloride 12g glucose 25.9g
Method: in sterilizing room,, add successively in proportion in the clean glass or rustless steel container, stir gently by described each component that takes by weighing of last table, fully mixed evenly after, fill in plastics or vial, warehouse-in, room temperature preservation gets final product.
It is 1-40% that this proportioning is used to make the oral drugs additive capacity.Add the oral drugs of this proportioning, can treat all kinds of oral disease, respiratory tract disease and the acute or chronic gastritis that cause by bacterial infection.Implement four: make 100 gram composite lysostaphin preparation proportionings: the coccus enzyme 0.1g of Portugal, molten Portugal lysozyme 58g bacteriostatic peptide 15g potassium phosphate 14g sodium chloride 12.9g
Method: in sterilizing room,, add successively in proportion in the clean glass or rustless steel container, stir gently by described each component that takes by weighing of last table, fully mixed evenly after, fill in plastics or vial, warehouse-in, room temperature preservation gets final product.
This proportioning is used to make the otitis disease drug, and additive capacity is 1-20%; Add the auditory meatus medicine of this proportioning, can treat all kinds of inflammations of external auditory canal, otitis media.Be used to make ophthalmic remedy, additive capacity is 1-20%; The opthalmological that adds prescription four can be used for treating keratitis, orbital cellulitis, conjunctivitis, hordeolum; Be used to remove adherent antibacterial on the recessive glasse.Be used for the aquatic product fishery medicine, additive capacity is 15-40%; Can be used for treating the bacterial disease of Aquatic product.Be used to make cosmetics, additive capacity is 1-20%, can be used for preventing and treating acne, treats all kinds of by antibacterial, fungus-caused skin of face illness.Implement five: make 100 gram composite lysostaphin preparation proportionings: the coccus enzyme 0.1g of Portugal, molten Portugal lysozyme 58g ephedrine 15g potassium phosphate 14g sodium chloride 12.9g
Method: in sterilizing room,, add successively in proportion in the clean glass or rustless steel container, stir gently by described each component that takes by weighing of last table, fully mixed evenly after, fill in plastics or vial, warehouse-in, room temperature preservation gets final product.
This prescription can be used for making the nasal inflammation medicine, and additive capacity is 1-20%, can treat acute and chronic rhinitis, sinusitis.
Claims (7)
1. the complex preparation of a staphylococcus lysozyme is characterized in that said preparation forms 100% form by 0.1-20% staphylococcus lysozyme, 50-85% lysozyme, 1-20% antibacterial, 0.5-20% ionic compound, 0.2-30% glucosamine material, 0-20% ephedrine and 0.1-20% antistaling agent with arbitrary proportion.
2. a kind of lysostaphin compounded preparation according to claim 1 is characterized in that wherein said antibacterial is hibitane or bacteriostatic peptide; Ionic compound is K
+, Na
+, Mg
2+, PO
4-, Cl
-In 2 kinds combination; The glucosamine material is chitin, chitosan or N-acetyl-D-amino; Antistaling agent is parabens or sodium benzoate.
3. the preparation method of a lysostaphin compounded preparation as claimed in claim 1, it is characterized in that this method is in sterilizing room, take by weighing each component by above-mentioned each prescription, add in the clean glass or rustless steel container in proportion successively, stir gently, fully mixed evenly after, fill is in plastics or vial, warehouse-in, room temperature preservation gets final product.
4, the application of a kind of molten Portugal as claimed in claim 1 coccus compound enzyme complex preparation in the preparation biofungicide is characterized in that said preparation can make an addition to external pharmaceutical preparation, food preservative, oral drug preparation, ear medicine, nose medicine, fisheries drug and cosmetics of everyday use preparation.
5. the molten Portugal as claimed in claim 4 coccus compound enzyme complex preparation application in the preparation biofungicide, it is characterized in that said preparation to gonococcus, staphylococcus aureus, drug resistance staphylococcus aureus, staphylococcus epidermidis, Candida albicans, bacillus pyocyaneus, escherichia coli, drug resistance Diplococcus pneumoniae, Diplococcus pneumoniae, D group enterococcus, tetracoccus, product monokaryon Listerella, streptococcus, anaerobe, have a liking for the narrow food sporangium of Fructus Hordei Germinatus and stomach Helicobacter pylori has killing action.
6, the application of a kind of molten Portugal as claimed in claim 4 coccus compound enzyme complex preparation in the preparation biofungicide, it is characterized in that said preparation can make an addition to the treatment abscess, tinea, ulcer, decubital ulcer, burn, scald, burn, furuncle, incised wound, oral ulcer, vaginitis, all kinds of oral diseases that cause by bacterial infection, respiratory tract disease and acute or chronic gastritis, all kinds of inflammations of external auditory canal, otitis media, keratitis, orbital cellulitis, conjunctivitis, hordeolum, acute and chronic rhinitis, sinusitis, prevention of STD, the bacterial disease of Aquatic product, prevent and treat acne, all kinds of by antibacterial, in the medicine of fungus-caused skin of face illness etc.
7, the application of a kind of molten Portugal as claimed in claim 4 coccus compound enzyme complex preparation in the preparation biofungicide, it is characterized in that said preparation can be used for the debridement and the wound dressing of preoperative and postoperative in the various surgical operations such as surgery, department of obstetrics and gynecology, urology department, the department of stomatology, can be used for removing adherent antibacterial on the contact lens.
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|---|---|---|---|
| CN 02110672 CN1367018A (en) | 2002-01-28 | 2002-01-28 | Compound preparation of staphylococcolysis enzyme and its preparation method and application |
| CNB031034764A CN100450546C (en) | 2002-01-28 | 2003-01-27 | Compound preparation for dissolving staphyloase and preparation method |
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|---|---|---|---|
| CN 02110672 CN1367018A (en) | 2002-01-28 | 2002-01-28 | Compound preparation of staphylococcolysis enzyme and its preparation method and application |
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| WO2005120555A1 (en) * | 2004-06-10 | 2005-12-22 | Mi An | Use of human lysozyme in preparation of medicine for treating acne |
| WO2009150171A1 (en) * | 2008-06-10 | 2009-12-17 | Profos Ag | Method of treatment of inflammatory diseases |
| CN101537176B (en) * | 2008-03-21 | 2012-02-29 | 徐士清 | Application of staphylococcus lysozyme compound in preparing medicament improving animal health condition |
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| WO2005120555A1 (en) * | 2004-06-10 | 2005-12-22 | Mi An | Use of human lysozyme in preparation of medicine for treating acne |
| CN101537176B (en) * | 2008-03-21 | 2012-02-29 | 徐士清 | Application of staphylococcus lysozyme compound in preparing medicament improving animal health condition |
| WO2009150171A1 (en) * | 2008-06-10 | 2009-12-17 | Profos Ag | Method of treatment of inflammatory diseases |
| CN103705912B (en) * | 2013-12-20 | 2015-10-28 | 江苏雪豹日化有限公司 | A kind of composite lysozyme oral spray and preparation method thereof |
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| CN104606672A (en) * | 2014-12-11 | 2015-05-13 | 杨陈 | Staphylococcus-dissolving composite enzyme sterilization spraying agent and preparation method thereof |
| CN104524557A (en) * | 2014-12-16 | 2015-04-22 | 杨陈 | Lysostaphin compound disinfection gel |
| CN104721812A (en) * | 2014-12-16 | 2015-06-24 | 杨陈 | Lysostaphin compound enzyme disinfectant and preparation method thereof |
| CN106668850A (en) * | 2015-11-05 | 2017-05-17 | 惠众国际医疗器械（北京）有限公司 | Natural bactericides/antibacterial agents |
| CN109908344A (en) * | 2017-12-12 | 2019-06-21 | 广州汇高生物科技有限公司 | A pharmaceutical composition for treating ulcerative colitis and preparation method thereof |
| CN109481671A (en) * | 2018-12-11 | 2019-03-19 | 重庆灵方生物技术有限公司 | A kind of thimerosal and preparation method thereof |
| CN111298108A (en) * | 2020-04-10 | 2020-06-19 | 亘元(天津)生物医药科技有限公司 | Long-acting compound enzyme disinfection composition for children and application thereof |
| CN113440645A (en) * | 2021-06-29 | 2021-09-28 | 西安汇朴成医疗科技有限公司 | Composite lysozyme liquid dressing for wound surface and preparation method thereof |
| CN117717612A (en) * | 2023-12-19 | 2024-03-19 | 中山自然说生物科技有限公司 | Privacy care composition and preparation method and application thereof |
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